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Characterizing Stress Granule Regulation By Pas Kinase, Ataxin-2 And Ptc6 And Investigating The Lifespan Of Covid-19 Virus On Currency, Colleen R. Newey

Theses and Dissertations

The protein Ataxin-2 is a known positive regulator of stress granules in humans, mice and yeast (known as yeast PBP1). Due to the role that stress granules play in diseases including Amyotrophic Lateral Sclerosis (ALS) and cancer, this thesis investigates the role of Ataxin-2 and its protein binding partners in stress granule development and its effects on various metabolic phenotypes of the cell. PAS kinase is a sensory protein kinase, conserved from yeast to man, which regulates respiration and lipid biosynthesis. Our lab discovered that PAS kinase phosphorylates and activates Ataxin-2 in yeast, and that PAS kinase overexpression enhances localization …

The Effects Of Ketones On Brain Metabolism And Cognition, Erin Reiko Saito

Theses and Dissertations

The brain is one of the most energetically demanding organs within the human body and is cognitively susceptible to energetic deficits such that the rise in obesity, insulin resistance, and Alzheimer’s disease in recent decades pose a substantial threat to cognitive longevity. The therapeutic efficacy of ketones are well-established in epilepsy and are currently being applied to other disease states. Alzheimer’s disease is characterized by impairments in brain glucose uptake and metabolism in regions relevant to learning, memory, and cognition that progress with the disease. While brain glucose uptake is impaired, ketone uptake is unaltered, potentially enabling ketones to fuel …

Understanding The Relationship Among Cool Temperatures, Growth, Metabolism, And Energy Use Of Ictalurus Spp., Abby Vaughn

Theses and Dissertations

Although U.S. commercial catfish aquaculture ponds are in temperate regions and experience cool to cold temperatures during the winter, few studies have investigated the effects of low temperatures on catfish physiological processes. Therefore, growth, metabolism, swimming performance, and blood variables were compared between channel (Ictalurus punctatus), blue (I. furcatus), and hybrid (I. furcatus x I. punctatus) catfish at 10 and 20°C. Accelerometers were also used to evaluate relationships among acceleration, metabolism, and tail beat frequency (TBF) during swimming performance tests. Channel catfish experienced the greatest growth, yet growth was diminished across all fish types at 10°C. Metabolic processes, swimming performance, …

Regulation Of T Cell Activation By The Cd5 Co-Receptor And Altered Peptides, Characterization Of Thymidine Kinase-Specific Antibodies, And Integrating Genomics Education In Society, Kiara Vaden Whitley

Theses and Dissertations

Helper T cells (Th) are a vital component of the immune system responsible for directing other immune cells to eliminate pathogens and cancer. Specifically, Th cells facilitate B cell and cytotoxic T cell (Tc) activation and recruitment and enhance their function against cancer and infectious diseases. Th cells are a valuable resource for improving Tc responses in cancer treatment and have become a focus of immunotherapeutic research. While it is increasingly clear that helper T cells serve an important role, the details about which entities produce an effective Th cell response remain unclear. CD5 is a T cell co-receptor that …

The Effects Of Moderate And High Temperatures On Growth, Metabolism, And Blood-Oxygen Affinity In Ictalurus Spp., Brandon Gerhart

Theses and Dissertations

Despite the growing use of hybrid catfish (Ictalurus furcatus × I. punctatus) in aquaculture, few studies have investigated the comparative effects of temperature on physiological performance with other cultured catfish. Therefore, growth, metabolism, and blood-oxygen affinity of blue (I. furcatus), channel (I. punctatus), and hybrid catfish were compared at moderate (23°C) and high (33°C) water temperatures. Channel catfish had the greatest growth and were in better condition compared to blue and hybrid catfish. Hybrid catfish standard metabolic rates did not differ from blue or channel catfish, while hybrid catfish had higher maximum metabolic rates, …

Effects Of Temperature On Growth, Metabolic Rate, And Lower Dissolved Oxygen Tolerance Of Speckled Peacock Bass Cichla Temensis, Manuel E. Coffill-Rivera

Theses and Dissertations

I examined the effects of temperature (25, 30, and 35°C) on growth, standard metabolic rate (SMR), and lower dissolved oxygen tolerance (LDOT) of juvenile Speckled Peacock Bass Cichla temensis. Fish were acclimated to 150-L aquaria for 7 weeks before the growth, SMR, and LDOT experiments. The growth study lasted 58 days and fish acclimated to 25 and 30°C displayed similar growth rates, while fish acclimated to 35°C had very poor growth rates. The SMR and LDOT experiments were performed using intermittent respirometers. Fish acclimated to 25°C had the lowest SMR, followed by 30°C, and finally 35°C. The highest LDOT …

Varied Levels Of Fructose Consumption Induce Physiological, Cognitive, And Mitochondrial Alterations In Aged Female Rats, Emilie L. Bjerring

Theses and Dissertations

Since the 1970s, fructose consumption has dramatically increased within the United States, as well as the world. While adolescents tend to be the largest consumer of fructose, mostly seen in the form of sugary beverages, the consequences of a high fructose diet started in adulthood can also have severe implications on physiological parameters as well as cognition. Several studies have linked fructose consumption to metabolic syndrome, a clustering of symptoms related to overall health, with particular emphasis placed on obesity, type II diabetes, and the relationship with Alzheimer’s Disease. These findings largely stem from the outcomes of studies on cognition, …

Evolution And Selection: From Suppression Of Metabolic Deficiencies To Bacteriophage Host Range And Resistance, Daniel Kurt Arens

Theses and Dissertations

The evolution and adaptation of microorganisms is so rapid it can be seen in the time frame of days. The root cause for their evolution comes from selective environmental pressures that see organisms with beneficial mutations survive otherwise deadly encounters or outperform members of its population who fail to adapt. This does not always result in strict improvement of the individual as in the case of antibiotic resistant bacteria who often display fitness tradeoffs to avoid death (see Reviews [1-3]). For example, when an ampicillin resistance gene (ampC) containing plasmid that is occasionally found in the wild was transformed into …

Function Of Gpr68 In Normal Hematopoiesis And Malignant Hematopoietic Diseases, Xiaofei He

Theses and Dissertations

G protein-coupled receptor 68 (GPR68), as a proton-sensing receptor, is involved in numerous physiological processes. However, its specific functions in normal hematopoiesis and malignant hematopoietic diseases were unknown. Using a genetic loss of function approach (i.e. whole-body Gpr68^-/- mouse model), B lymphocytes were reduced under stressed conditions, such as aging and hematopoietic regeneration. However, hematopoietic stem cells (HSC) from Gpr68^-/- mice exhibited comparable function as HSC from wild type mice either under steady-state or upon stress. To determine whether the unaltered HSC function of Gpr68^-/- mice was due to compensatory effects of Gpr68 in nonhematopoietic cells, a …

Effect Of Water Consumption On Resting Metabolism In Adults, Brittany Leigh Murphy

Theses and Dissertations

This study analyzed the acute effect of water consumption on resting metabolic rate (RMR). It was hypothesized that water would have a small, nonclinically significant effect on RMR. Men and women ages 18–40 years participated in a crossover study in which each participant received a No Water and Water condition (order determined randomly) with a 7-day washout period between each condition. Both conditions began with visual analog scales to gauge hunger and thirst levels, urine spectrometry to quantify hydration status, and height and weight measurements. The No Water condition consisted of a 30-minute rest period followed by 45 minutes of …

The Role Of Beta-Hydroxybutyrate In Altering Adipose Mitochondrial Bioenergetics, Chase Mitchell Walton

Theses and Dissertations

The rampant growth of obesity worldwide has stimulated explosive research into human metabolism. Metabolic rate has been shown to be altered by diets differing in macronutrient composition, with low-carbohydrate, ketogenic diets eliciting a significant increase over other interventions. The purpose of this study was to determine the effects of the ketone β-hydroxybutyrate (βHB) on mitochondrial respiration and coupling status in adipose tissue. To explore this, we employed three distinct systems, namely cell, rodent, and human models. In every model, βHB robustly increased mitochondrial respiration. Furthermore, in cultured adipocytes and rodent adipose, we quantified the expression of genes involved in mitochondrial …

Genetic Determinants Of Variation In The Gh/Igf-1 Axis And Their Relationship To Cardiometabolic Health, Rafael Luis Aguirre Guillen

Theses and Dissertations

Background: In a study of Mexican Americans, we performed analyses of GEI and pleiotropy in the axis in relation to MS. GH/IGF-1 axis components were studied. Model parameters and likelihoods were estimated by maximum likelihood.

Results: Pleiotropy was observed for IGFBP3 (p

Conclusions: IGF-I and IGFBP3 are genetically correlated with MS whereas MS influences the additive genetic variance in IGFBP1 variables mainly but also in IGF-I somewhat by virtue of the VH exhibited by IGF-I/IGFBP1.

Investigation Of Therapeutic Immune Cell Metabolism, Josephine Anna Tueller

Theses and Dissertations

This thesis addresses multiple approaches to investigating mechanisms of immune linked disease. There are four projects outlined below which describe the work of these investigations. First, educating students about techniques to study disease and therapies is an important area of research. Flow cytometry is a common technique in immunology and its versatility and high throughput abilities can be applied to many fields. While it is very useful, flow cytometry is a complex technique that requires training to operate and understand, and there are very few reports about administering effective training. This thesis outlines the first report of a full semester …

Regulation Of Immune Cell Activation And Functionby The Nbmpp2 Protein Andthe Cd5 Co-Receptor, Claudia Mercedes Freitas

Theses and Dissertations

According to the centers for disease control and prevention (CDC) and the world healthorganization (WHO), heart disease and immune related diseases such as diabetes and cancer areamong the leading causes of death around the world. Thus, the regulation of the function ofimmune cell plays a key role in health and disease. Calcium (Ca2+) ions play a critical role inimmune cell activation, function and in a robust immune response. Defects in Ca2+ signalinginfluences the development of cardiac disease, Alzheimer disease, immune cell metabolism,muscle dysfunction, and cancer. Each immune cell is unique in its activation and function,making it relevant to understand how …

Assessment Of Microbial Carbon Processing And Its Implications To The Carbon Budget Of Lake Superior, Lindsey Michelle Koren

Theses and Dissertations

Over the past few decades, there has been increased research focus on carbon cycling within aquatic systems, especially with the changing global climate. Inland waters play a major role in the global carbon cycle, but the fundamental features remain poorly understood, particularly the large lakes of the world. Our experimental approach assessing the carbon budget of Lake Superior, the largest freshwater lake by area, provides spatial and temporal variability that has been previously overlooked but may be critical to our understanding on the biogeochemical processes controlling the lake. Multiple stations were chosen across the lake, both nearshore and offshore, to …

Gut Microbiota Regulates The Interplay Between Diet And Genetics To Influence Insulin Resistance, Jeralyn Jones Franson

Theses and Dissertations

Insulin resistance and obesity are major public health concerns. The impact of diet and genetics on insulin resistance and obesity is well accepted. Additionally, the gut microbiota has been shown to influence obesity and metabolic disorders. However, much remains to be understood about the role of gut microbiota in the development of insulin resistance and obesity. We utilized a mouse model lacking PAS kinase, a protein involved in cellular metabolism, in order to better understand the relationship between diet, genetics and the gut microbiota. Previous research has shown that mice lacking PAS kinase were protected from the effects of a …

Investigating The Role Of Zinc In The Physiology And Virulence Of Streptococcus Pneumoniae, Lindsey Renae Brown-Burcham

Theses and Dissertations

Homeostasis of trace metal ions is essential for a variety of cellular processes and virulence mechanisms, including resistance to oxidative stress, DNA replication, and regulation of cell adhesion/invasion. Understanding how pathogenic microorganisms overcome metal starvation and intoxication provides insight into how these mechanisms could be targeted by novel antimicrobial therapies. Streptococcus pneumoniae, or pneumococcus, is a Gram-positive, commensal of the human nasopharynx and upper respiratory tract. Though this organism is primarily an asymptomatic colonizer, it is also the causative agent of infections ranging in severity from reoccurring acute otitis media to life-threatening community acquired pneumonia or bacterial sepsis. This study …

Metabolic Dysregulation: An Investigation Of The Role Of Foxo3 In Gluconeogensis In Pten-Null Glioblastomas, Victor Fanniel

Theses and Dissertations

Many processes are regulated by the Phosphatidylinositol 3 kinase (PI3K) pathway in the cell including cell survival, metabolism, and apoptosis. Increased activation of the PI3K pathway is a hallmark of many cancers which can be oftentimes attributed to the mutation of PTEN, which encodes an enzyme that performs the reverse reaction of PI3K. When PTEN is null-mutated, this creates a constitutively active PI3K pathway and constitutively active AKT. Since AKT phosphorylates conserved residues on FOXO transcription factors to mark them for nuclear export, this renders FOXO inactive. However, new research has provided evidence that FOXO is still present in …

Monitoring Expression Of Metabolic Genes During The Hypoxic Response Of S. Cerevisae, Nikkoli Lueder

Theses and Dissertations

All organisms appear to have the ability to sense and respond to changes in their environment. Hypoxia, or low oxygen, is experienced by many organisms at some point in their life cycle. Some organisms such as S. cerevisiae, a species of yeast, respond by dramatically altering gene expression. The result is that genes needed in the new environment are turned on and unneeded genes are turned off. S. cerevisiae has been used in our study because it shares many genes with other eukaryotes, including humans, so many of our findings are applicable to these organisms. Here, we tried to understand …

Glycolytic Atp Production Is Required For Innate Mast Cell Activation And Is Limited By Lactic Acid, Which Effectively Reduces Lps-Induced Cytokine Production In Mast Cells And In Vivo, Heather Caslin

Theses and Dissertations

The metabolic pathways required for adenosine triphosphate (ATP) production within the cell are well understood, however recent publications suggest that metabolic pathways are closely linked to immune cell activation and inflammatory diseases. There has been little examination of the metabolic pathways that modulate mast cell activation and the feedback regulator lactic acid. Here we examine metabolic pathways and regulation within mast cells in the context of lipopolysaccharide (LPS) and interleukin (IL-33) activation, for which there has been little to no reported studies. First, we examine the effects of lactic acid, previously considered only a by-product of glycolysis and now understood …

Effects Of The Na-Cl Co-Transporter (Ncc) In Western Diet Induced Metabolic And Cardiac Dysfunction, Zachary S. Cutter

Theses and Dissertations

Interleukin-18 (IL-18) is a pro-inflammatory cytokine known to be involved in maintaining metabolic homeostasis; however, also capable of inducing cardiac dysfunction. Additionally, IL-18, has been shown to bind to a novel receptor, the Na-Cl Co-transporter (NCC). We hypothesized that NCC mediates IL-18 metabolic and cardiac signaling in mice. Using male C57BL/6J mice, we compared the metabolic and cardiac function changes after at least 8 weeks of high-saturated fat high sugar diet (Western Diet) in NCC knockout (NCCKO), IL-18 knockout (IL-18KO), and wild-type mice. We show that NCCKO mice have significantly increased body weight gain from baseline, no difference in fasting …

Discovery And Characterization Of Bile Acid And Steroid Metabolism Pathways In Gut-Associated Microbes, Spencer Harris

Theses and Dissertations

The human gut microbiome is a complex microbial ecosystem residing in the lumen of our gastrointestinal tract. The type and amounts of microbes present in this ecosystem varies based on numerous factors, including host genetics, diet, and environmental factors. The human gut microbiome plays an important role in normal host physiological functions, including providing energy to colonocytes in the form of short-chain fatty acids. However, gut microbial metabolites have also been associated with numerous disease states. Current tools for analyzing the gut microbiome, such as high-throughput sequencing techniques, are limited in their predictive ability. Additionally, “-omic” approaches of studying the …

A Comparison Of Computational Methods For Estimating Estuarine Production And Respiration From Diel Open Water Dissolved Oxygen Measurements, Spencer Tassone

Theses and Dissertations

Diel dissolved oxygen (DO) data were used to characterize seasonal, inter-annual, and longitudinal variation in production and respiration for the James River Estuary. Two computational methods (Bayesian and bookkeeping) were applied to these data to determine whether inferences regarding DO metabolism are sensitive to methodology. Net metabolism was sensitive to methodology as Bayesian results indicated net heterotrophy (production < respiration) while bookkeeping results indicated net autotrophy (production > respiration). Differences in net metabolism among the methods was due to low seasonal variation in respiration using the Bayesian method, whereas bookkeeping results showed a strong correlation between production and respiration. Bayesian results suggest a dependence on allochthonous organic matter (OM) whereas …

The Role Of Hypoxia On Pyruvate Kinase M2, Mammalian Target Of Rapamycin, Mitochondrial Function, And Cell Invasion In The Trophoblast, Rebecca Lutz Kimball

Theses and Dissertations

This thesis will be organized into two chapters discussing the role of hypoxia in the human placenta. The goal of this thesis is to characterize pyruvate kinase M2, mammalian target of rapamycin, mitochondrial function, and cell invasion in hypoxic conditions in the trophoblast. Understanding the mechanisms of placental metabolism can lead to further treatments for placental diseases. Chapter one covers the background of intrauterine growth restriction, hypoxia, placental metabolism, and pyruvate kinase M2 (PKM2). Little is currently understood about the role of the mitochondria in placental diseases. Expression of PKM2, trophoblast cell invasion, and mitochondrial function is shown to be …

Effect Of Dietary Lysine On Plasma Amino Acid Profile And Selected Metabolites Of Late-Stage Finishing Pigs, Naresh Regmi

Theses and Dissertations

The objective of this study was to evaluate the effects of dietary lysine on plasma concentrations of amino acid (AAs) and other metabolites of finishing pigs. Eighteen crossbred late-stage finishing pigs (9 barrows and 9 gilts) were assigned to three dietary treatments, Diets I (lysine-deficient), II (lysineequate), and III (lysine-excess), according to a randomized complete block design with gender as block. After 4 weeks on trial, jugular vein blood were collected and centrifuged for plasma samples, which were analyzed for concentrations of 24 AAs using HPLC method and 6 selected metabolites related to major nutrient metabolism using ACE Alera Clinical …

Identifying And Characterizing Yeast Pas Kinase 1 Substrates Reveals Regulation Of Mitochondrial And Cell Growth Pathways, Desiree Demille

Theses and Dissertations

Glucose allocation is an important cellular process that is misregulated in the interrelated diseases obesity, diabetes and cancer. Cells have evolved critical mechanisms for regulating glucose allocation, one of which is sensory protein kinases. PAS kinase is a key sensory protein kinase that regulates glucose allocation in yeast, mice and man; and is a novel therapeutic target for the treatment of metabolic diseases such as obesity, diabetes and cancer. Despite its importance, the molecular mechanisms of PAS kinase function are largely unknown. Through large-scale protein-interaction studies, we have identified 93 novel binding partners for PAS kinase which help to expand …

A Comparison Of Obesity Interventions Using Energy Balance Models, Marcella Torres

Theses and Dissertations

An energy balance model of human metabolism developed by Hall et al. is extended to compare body composition outcomes among standard and proposed obesity interventions. Standard interventions include a drastic diet or a drastic diet with endurance training. Outcomes for these interventions are typically poor in clinical studies. Proposed interventions include a gradual diet and the addition of resistance training to preserve lean mass and metabolic rate. We see that resistance training, regardless of dietary strategy, achieves these goals. Finally, we observe that the optimal obesity intervention for continued maintenance of a healthy body composition following a diet includes a …

The Role Of Intermembrane Space Redox Factors In Glutathione Metabolism And Intracellular Redox Equilibrium, Hatice Kubra Ozer

Theses and Dissertations

The mitochondrial intermembrane space (IMS) is a unique subcellular compartment that houses key thiol-dependent redox pathways such as protein transport, mitochondrial respiration, and detoxification of ROS (reactive oxygen species). These pathways are all dependent on cysteine-rich proteins, thus maintaining thiol-disulfide balance in this organelle is crucial for cellular functions. An IMS protein import pathway called the Mia40-Erv1 disulfide relay system uses disulfide bond formation for the import and retention of substrate proteins in the IMS. Erv1 is also suggested to be involved in maturation of cytosolic Fe-S cluster proteins and regulation of iron homeostasis in S. cerevisiae. However, these studies …

Global Climate Change And The Southern Ocean: How Antarctic Fishes Physiologically Respond To A Changing Environment From The Cellular To The Organismal Level, Laura A. Enzor

Theses and Dissertations

Studies have projected that future changes in sea surface temperature and pCO2 levels will impact higher latitudes to a greater extent than in temperate regions. For notothenioid fishes of the Southern Ocean, evolution in extremely stable, cold waters has resulted in several adaptations which have left these fishes poorly prepared for global climate change. I have analyzed the metabolic and cellular response of Trematomus bernacchii, Pagothenia borchgrevinki and Trematomus newnesi to a long-term, multi-stressor scenario relevant to the predicted changes in the Southern Ocean. By combining whole animal respirometry with cellular level analysis of energy allocation, osmoregulatory mechanisms and cellular …

Different Expression Of Placental Pyruvate Kinase M2 In Normal, Preeclamptic, And Intrauterine Growth Restriction Pregnancies, Brigham L. Bahr

Theses and Dissertations

This thesis will be organized into two chapters discussing the placental expression of two proteins, pyruvate kinase M2 (PKM2) and heat shock protein 27 (HSP 27), in human placentas. Understanding the mechanisms of placental metabolism in healthy and diseased placentas helps us understand how placenta disorders occur and how we can treat these disorders. The goal is to investigate these proteins to gain an understanding of their roles in placental disorders and help decrease maternal and fetal mortality rates. Chapter one covers the background of pyruvate kinase M2 (PKM2) in cancer and embryonic tissues, and the expression of PKM2 in …